losartan-potassium and Erectile-Dysfunction

Erectile dysfunction (ED) following treatment for clinically localized prostate cancer, particularly radical prostatectomy (RP), is a major quality of life issue that remains unsatisfactorily addressed. With the introduction and use of cavernous nerve-sparing procedures over the past 25 years, many men recover erections postoperatively that enable sexual intercourse unlike in the prior surgical era, when permanent ED postoperatively was certain. Despite this advance, 26-100% of these patients may never recover normal erectile function (EF). Recent advances in the understanding of ED after RP have stimulated great attention to develop penile rehabilitation programs and neuromodulation. The purpose of penile rehabilitation is to prevent adverse corpus cavernosal tissue structural alterations and thereby maximize the chances of recovering functional erections. Rehabilitation programs are common in clinical practice, but there is no definitive evidence to support their efficacy. Neuromodulation represents another strategy for promoting erection recovery postoperatively. This therapy involves the application of neuroprotective interventions, conceivably targeting biological elements involved in the erection response that are affected by neuropathic injury. Well-conducted, controlled trials with adequate follow-up are required in order to determine the erection preservative benefits of these therapeutic strategies. The purpose of this essay is to describe the mechanisms related to post-RP ED, assess the need for penile rehabilitation and neuromodulation following surgery, and analyze the basic science and clinical trial evidence associated with these applications for preserving EF following prostate cancer treatment.

Topics: Anti-Inflammatory Agents; Electrodes; Erectile Dysfunction; Erythropoietin; Genetic Therapy; Humans; Ligands; Male; Penis; Phosphodiesterase Inhibitors; Prostaglandins; Prostatectomy; Vacuum

Advances in the neurobiology of growth factors, neural development, and prevention of cell death have resulted in a heightened clinical interest for the development of protective and regenerative neuromodulatory strategies for the cavernous nerves (CNs), as therapies for prostate cancer and other pelvic malignancies often result in neuronal damage and debilitating loss of sexual function. Nitric oxide released from the axonal end plates of these nerves within the corpora cavernosa causes relaxation of smooth muscle, initiating the haemodynamic changes of penile erection as well as contributing to maintained tumescence; the loss of CN function is primarily responsible for the development of erectile dysfunction (ED) after pelvic surgery and serves as the primary target for potential neuroprotective or regenerative strategies. Evidence from pre-clinical studies for select neuromodulatory approaches is reviewed, including neurotrophins, glial cell line-derived neurotrophic factors (GDNF), bone morphogenic proteins, immunophilin ligands, erythropoetin (EPO), and stem cells.

Topics: Animals; Bone Morphogenetic Proteins; Brain-Derived Neurotrophic Factor; Erectile Dysfunction; Erythropoietin; Glial Cell Line-Derived Neurotrophic Factor; Growth Differentiation Factor 5; Humans; Immunophilins; Male; Nerve Growth Factors; Neurotransmitter Agents; Penis; Peripheral Nerve Injuries; Postoperative Complications; Stem Cell Transplantation

Erectile dysfunction significantly impacts quality of life for men undergoing radical prostatectomy for prostate cancer. Erythropoietin is a promising neurotrophic factor for neurogenic erectile dysfunction based on preclinical and retrospective data.. ERECT (NCT00737893) is a phase 2, double-blinded, randomized, placebo-controlled trial (July 2017-December 2019) evaluating the impact of perioperative erythropoietin on recovery of erectile function and other patient-reported, health-related quality of life outcomes after bilateral nerve-sparing radical prostatectomy (3, 6, 9, and 12 months). Erythropoietin (20,000 units) or saline placebo was injected subcutaneously the day before, day of, and day after surgery for 3 total doses.. Of 63 patients assessed for eligibility, 56 patients were randomized. Arms (29 erythropoietin, 27 placebo) were well balanced (89.3% robotic, median age 55.5 years). International Index of Erectile Function-Erectile Function Domain (IIEF-EF) scores increased from median 12.5 at 3 months to 24.5 at 12 months. Median 2-week serum hemoglobin was higher for the erythropoietin arm compared to placebo (14.7 vs 13.6, p=0.02). There was no statistically significant difference in IIEF-EF scores at 6 months comparing erythropoietin to placebo (p=0.50) or at other time points (mixed model regression coefficient: -1.7, 95% CI -6.1-2.7, p=0.45). Excellent nerve-sparing rating (10/10) was associated with improved IIEF-EF recovery (+5.2, p=0.022). Other patient-reported, health-related quality of life domains as well as oncologic outcome and complications were similar between arms during followup.. In the context of brief perioperative dosing, erythropoietin did not improve recovery of erectile function for men undergoing radical prostatectomy for prostate cancer compared to placebo. Further research to identify effective adjuncts to improve health-related quality of life for these men is needed.

Topics: Double-Blind Method; Erectile Dysfunction; Erythropoietin; Humans; Male; Middle Aged; Postoperative Complications; Prospective Studies; Prostatectomy; Prostatic Neoplasms; Quality of Life; Recovery of Function; Treatment Outcome

Erythropoietin receptors have been localized to human penile tissue and periprostatic neurovascular bundles. ERECT is a placebo-controlled, phase 2, randomized trial assessing the effect of erythropoietin on recovery of erectile function for men undergoing radical prostatectomy for prostate cancer.

Topics: Clinical Trials, Phase II as Topic; Erectile Dysfunction; Erythropoietin; Humans; Male; Postoperative Complications; Prostatectomy; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Recovery of Function

Recombinant human erythropoietin (rHuEPO) was administered to males undergoing hemodialysis, and its effects on penile erection and hypothalamus-pituitary-gonadal hormone levels were studied. The subject consisted of 18 males undergoing hemodialysis ranging in age from 22 to 58 years (mean 45.3 years). Chronic glomerulonephritis was present in 16, and diabetic nephropathy in 2, as underlying disease. rHuEPO was administered intravenously at 1,500 U 3 times a week with a target to increase the Ht value to 25% or above. Penile erection was evaluated subjectively by a questionnaire based on a visual analogue scale and objectively by semi quantitative measurement of nocturnal penile tumescence (NPT) using an erectometer. Of the 18 patients, subjective improvements in penile erection were observed in 13 (72%), and objective improvements in NPT were observed in 10 (56%). The administration of rHuEPO may alleviate hyperprolactinemia but was found to have no effect on the FSH, LH, Zn, or HS-PTH level. rHuEPO was suggested to be fairly effective for the treatment of sexual disorders.

Topics: Adult; Chronic Disease; Diabetic Nephropathies; Erectile Dysfunction; Erythropoietin; Glomerulonephritis; Humans; Hypothalamo-Hypophyseal System; Male; Middle Aged; Penile Erection; Recombinant Proteins; Renal Dialysis; Testis

Erectile dysfunction persists as a major functional complication of nerve-sparing radical prostatectomy.. To evaluate retrospectively the potential benefit of erythropoietin administration to improve erectile function recovery following radical prostatectomy.. Preoperatively potent patients who underwent nerve-sparing radical retropubic prostatectomy between March 2005 and February 2006 elected to receive erythropoietin treatment (40,000 IU subcutaneously, single injection on their preoperative day; treatment group, N = 15). A contemporaneous clinically matched cohort comprising patients who elected postoperative standard surveillance only served for comparison (control group, N = 21). Phosphodiesterase type 5 (PDE5) inhibitor "on-demand" use was applied. Potency evaluations were monitored by International Index of Erectile Function-5 questionnaires administered preoperatively and at 3, 6, and 12 months postoperatively.. Erection recovery.. Health comorbidities as well as erectile function status were demonstrated to be no different between groups at baseline. Erythropoietin-treated patients demonstrated significantly higher postoperative International Index of Erectile Function-5 questionnaire scores than control group patients at 3, 6, and 12 months postoperatively with or without use of PDE5 inhibitors (P < 0.05). At 12 months postoperatively, the percentages of patients performing sexual activity were 87% and 68% of erythropoietin-treated and control patients, respectively (P = 0.213), although the erythropoietin-treated patients had a significantly greater ability to perform sexual intercourse with minimal or no difficulty (P < 0.05).. Erythropoietin administration on the preoperative day before undergoing nerve-sparing radical prostatectomy in men reporting normal erectile function preoperatively may confer improved erectile function recovery postoperatively.

Topics: Adaptation, Physiological; Erectile Dysfunction; Erythropoietin; Health Status Indicators; Humans; Male; Middle Aged; Penile Erection; Penis; Prostatectomy; Recombinant Proteins; Severity of Illness Index; Surveys and Questionnaires

We investigated the effects of recombinant human (rh) erythropoietin (EPO) on erectile function recovery in a rat model of cavernous nerve (CN) injury.. Male rats underwent unilateral CN transection and excision of a 5 mm segment of the contralateral CN. One group received rhEPO (5,000 U/kg) subcutaneously daily for 14 days, while another received rhEPO 1 day and 1 hour prior to nerve injury. An additional group of animals was pretreated with 1 dose of darbepoetin (25 microg/kg). At 14 days following CN injury rats underwent erection physiology studies. Axonal regeneration was evaluated by electron microscopy. EPO receptor expression in the penis and major pelvic ganglion was evaluated immunohistochemically and by real-time polymerase chain reaction.. Daily rhEPO effectively recovered erections after CN injury compared with saline treatment. Maximal intracavernous pressure area under the curve normalized to mean arterial pressure was significantly greater in EPO treated vs saline treated animals (p < 0.05). rhEPO and darbepoetin pretreatment was as effective as continuous 14-day therapy. EPO receptor expression was localized to neuronal cell bodies of the major pelvic ganglion, penile nerves and endothelial cells in the penis. Electron microscopy revealed significant improvement in axonal regeneration in rhEPO treated animals 14 days following injury compared to controls.. EPO receptors are expressed in local neuronal and vascular tissues. Exogenous administration of rhEPO or darbepoetin in the setting of CN injury promotes erectile function recovery. This occurs through axonal regeneration of the injured nerve and possible penile protection.

Topics: Analysis of Variance; Animals; Base Sequence; Biopsy, Needle; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Erectile Dysfunction; Erythropoietin; Immunohistochemistry; Male; Microscopy, Electron; Molecular Sequence Data; Nerve Regeneration; Penis; Probability; Random Allocation; Rats; Rats, Sprague-Dawley; Receptors, Erythropoietin; Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction; Sensitivity and Specificity

Erythropoietin (rHuEpo) therapy has been shown to improve sexual function in the male dialysis population, with several studies suggesting a direct effect upon endocrine function, as well as correction of anaemia. Nevertheless many male dialysis patients receiving rHuEpo continue to complain of sexual dysfunction.. At a dedicated renal impotence clinic, 65 male dialysis patients were screened for endocrine disturbances. Baseline serum sex hormones were compared between those receiving and not receiving rHuEpo, using either the two-sample t test or the Mann-Whitney U test, after assessing for normality. Results from four patients were excluded on account of either medications (antiemetic phenothiazines), hepatic dysfunction, or carcinomatosis.. Twenty-five patients (41.0%) were receiving rHuEpo, the recipients and non-recipients being well matched for haemoglobin (10.19 +/- 0.29 vs 10.55 +/- 0.25 g/dl, n.s.), age (51.1 +/- 1.9 vs 53.6 +/- 2.1 years, n.s.) and duration of sexual dysfunction (median, 3.0 vs 3.0 years, n.s.). The rHuEpo recipients had a higher median creatinine (1090 vs 972 micromol/l, P < 0.02), but similar nutritional status to the non-recipients (albumin 41.0 vs 39.0 g/l, n.s.). The total duration of rHuEpo therapy was 0.85 +/- 0.14 years. Prolactin levels were similar in both the rHuEpo recipients and non-recipients (440 vs 541 mu/l, n.s.), as were LH (11.0 vs 10.5 iu/l, n.s.) and FSH (8.0 vs 6.5 iu/l, n.s.). However, there were significant elevations of testosterone (19.8 +/- 1.3 vs 16.1 +/- 1.1 nmol/l, P < 0.05) and sex hormone binding globulin (SHBG) (40.5 vs 26.0 nmol/l, P < 0.01), with a trend toward elevated oestradiol (304 vs 248 pmol/l, P = 0.095) in the rHuEpo-treated group. Forty-eight subjects (78.7%) received peritoneal dialysis (PD), with the 19 rHuEpo recipients (39.6%) demonstrating increased serum testosterone (21.0 +/- 1.5 vs 16.6 +/- 1.3 nmol/l, P < 0.05), SHBG (40.5 vs 26.5 nmol/l, P < 0.01), LH (15.0 vs 10.0 iu/l, P < 0.01) and FSH (12.0 vs 5.3 iu/l, P < 0.05). These differences were not demonstrated in the 13 haemodialysis (HD) subjects.. Male dialysis patients complaining of sexual dysfunction after correction of anaemia with rHuEpo are characterized by higher levels of serum testosterone and SHBG, but not suppression of hyperprolactinaemia or hyperoestrogenism. Male PD subjects receiving rHuEpo also demonstrated increased LH and FSH.

Topics: Aged; Anemia; Erectile Dysfunction; Erythropoietin; Estradiol; Follicle Stimulating Hormone; Humans; Kidney Failure, Chronic; Luteinizing Hormone; Male; Middle Aged; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Recombinant Proteins; Renal Dialysis; Sex Hormone-Binding Globulin; Sexual Dysfunction, Physiological; Testosterone

Six male dialysis patients were submitted to a Doppler study of the deep penile arteries and intracavernosal injection of 30 mg papaverine under basal conditions before and after erythropoietin therapy. Penile tumescence was recorded after 15 min by measuring the length and the circumference of the penis as well as the erectile angle between the penis and the legs with the patient in standing position. Haematocrit was raised by erythropoietin therapy from 19.3 +/- 4.5 to 31.2 +/- 5.5 within 3 months. Five patients completed the study. We encountered a significant improvement in the frequency of sexual intercourse per month from 1.3 +/- 0.5 to 2.3 +/- 0.8 (p = 0.014). Furthermore, an increase was observed in the penile brachial index (from 0.87 +/- 0.1 to 0.91 +/- 0.1) and in the papaverin induced increase in penile length (4.6 +/- 1.4 cm versus 5.2 +/- 1.1 cm), penile circumference (2.7 +/- 0.14 cm versus 2.7 +/- 0.27 cm) as well as in the erectile angle (61.7 +/- 37.1 versus 80 +/- 23.5 degrees). These changes were not statistically significant. There was a significant correlation between the increase in the erectile angle and the increase in frequency of intercourse (p = 0.04). In conclusion, erythropoietin treatment could improve the sexual potency in uraemic patients under chronic haemodialysis therapy.

Topics: Adult; Erectile Dysfunction; Erythropoietin; Hemoglobinometry; Humans; Kidney Failure, Chronic; Male; Papaverine; Penile Erection; Recombinant Proteins; Renal Dialysis; Sexual Behavior

Topics: Adult; Blood Viscosity; Erectile Dysfunction; Erythropoietin; Hematocrit; Humans; Male; Middle Aged; Renal Dialysis

Correction of anemia in long-term hemodialysis patients by recombinant human erythropoietin (r-HuEPO) has been reported to improve sexual function. As elevated serum prolactin levels are believed to contribute to altered sexual function in uremia, we followed serum prolactin and testosterone levels during four months of r-HuEPO therapy. Within these four months, hematocrit values rose from 23.7 +/- 1.2 to 35.7 +/- 0.2% and hemoglobin from 7.3 +/- 0.3 to 11.3 +/- 0.4 g/100 ml. In parallel, serum prolactin values decreased significantly, from 66.9 +/- 9.3 to 9.6 +/- 2.6 ng/ml in females and from 39.5 +/- 10.5 to 10.3 +/- 1.0 ng/ml in male dialysis patients. Testosterone concentrations were in the lower normal range in male patients and remained unchanged during r-HuEPO therapy. Sexual function improved in four out of seven males, and five out of nine female patients started to have regular menstruations again. It appears that treatment of anemia in end-stage renal disease by r-HuEPO may improve sexual function by lowering elevated serum prolactin concentrations.

Topics: Adult; Anemia; Erectile Dysfunction; Erythropoietin; Female; Humans; Hyperprolactinemia; Kidney Failure, Chronic; Libido; Male; Menstruation; Prolactin; Recombinant Proteins; Renal Dialysis; Testosterone

As it was reported that correction of anemia in long-term hemodialysis patients by recombinant human erythropoietin (r-HuEPO) is associated with improved sexual function, we conducted the present study to further delineate the mechanism(s) by which this is brought about. Serum prolactin, testosterone, and parathyroid hormone (PTH) levels were followed during 4 months of r-HuEPO therapy. Within 4 months of treatment with r-HuEPO, hematocrit values rose from 23.7 +/- 1.2 to 35.7 +/- 0.2% and hemoglobin increased from 7.3 +/- 0.3 to 11.3 +/- 0.4 g/100 ml. In parallel, serum prolactin values decreased significantly from 66.9 +/- 9.3 to 9.6 +/- 2.6 ng/ml in females and from 39.5 +/- 10.5 to 10.3 +/- 1.0 ng/ml in male dialysis patients. Testosterone concentrations were low in male patients and remained unchanged during r-HuEPO therapy. Baseline PTH values were elevated (1,880 +/- 220 pg/ml) in patients of both sexes and declined to 1,410 +/- 180 pg/ml during treatment with r-HuEPO. However, this difference did not reach statistical significance. Sexual function improved in 4 out of 7 males and 5 out of 9 female patients began to menstruate regularly again. It appears that treatment of anemia in end-stage renal disease by r-HuEPO improves sexual function via normalization of elevated serum prolactin concentrations.

Topics: Adult; Anemia; Erectile Dysfunction; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Male; Menstruation; Menstruation Disturbances; Parathyroid Hormone; Prolactin; Recombinant Proteins; Renal Dialysis; Testosterone